Biomedical subjects
Publications and source records attributed to R Ray.
Analysis of work profiles of 138 persons who had published in the Journal of the American Statistical Association showed this study group published more often than 128 members of the Association and tended to enjoy research, being less interested in the theoretical contribution of their work and more interested in the likelihood of work being published. Administrative and committee duties were impediments for those who published.
Before setting up the first Senior Citizens' Health Care Centre (SCHCC), a survey was done to establish the health and morbidity profiles of older adults in the community and their health care needs. Community volunteers personally interviewed 1,697 persons aged 55 years and above, living in three areas in Singapore. The response rate was 75%. The respondents' general characteristics, the prevalence rate of chronic diseases, their functional and mobility status, utilisation of the health services and how the chronic diseases affected their activities of daily living (ADL) were studied. Among the respondents, 2.1% required nursing care, 4.2% were unable to climb stairs, and 23.3% were on long-term medications. As compared to the younger age groups, those 75 years and above reported more difficulties with mobility (semi-ambulant 6.5%, bedridden 1.8%), more needed assistance in ADL (bathing 4.8%, toiletting 4.7%, dressing 3.0%, and feeding 2.4%) and a higher percentage required nursing care (3.6%). Services that would benefit the frail elderly are reported in this paper.
Overexpression of a transfected c-myc gene under the control of a strong promoter causes the phenotypic changes of malignant transformation. We have investigated the effect of exogenous c-myc gene expression in NIH3T3 cells transfected with an intact human c-myc gene which is expressed under the control of its own promoter. The presence of the exogenous c-myc gene in the transfected cells was documented by Southern blot analysis. The transfected clones contained 20-40 copies of the human c-myc gene and demonstrated a proportional elevation in the level of c-myc mRNA which had a normal half life of 20-30 min. Despite the high level of c-myc mRNA, the transfected cells contained a relatively low level of c-myc protein and expression appears to be regulated at a post-transcriptional level. The transfected cells exhibited a decreased serum requirement for growth and formed colonies in soft agar, but were non-tumorigenic in Balb/c athymic nude mice. The morphologic evidence of transformation in the absence of tumorigenesis suggests that transfection of murine fibroblasts with multiple copies of the c-myc gene expressed under the control of its own promoter may cause partial transformation.
An enzymatic activity that specifically hydrolyzes the highly toxic organophosphorus anticholinesterase compound soman (pinacolyl methylphosphonofluoridate) has been identified and partially characterized in the clonal neuronal neuroblastoma-glioma hybrid NG108-15 cell line. Using the whole cell homogenate as the enzyme source and 1 mM substrate, the relative rate of hydrolysis of two other toxic anticholinesterase compounds sarin (isopropyl methylphosphonofluoridate) and tabun (ethyl-N-dimethyl phosphoramidocyanidate) is approximately one-tenth the rate of hydrolysis of soman, while DFP (diisopropyl phosphorofluoridate), paraoxon (p-nitrophenyl diethylphosphate), and a phosphinate PNMPP (p-nitrophenyl methyl (phenyl) phosphinate) are not hydrolyzed. Analysis of the kinetics of soman hydrolysis reveals two components of the enzyme activity with different affinities and reaction rates. Unlike previously reported enzymes of this type, this enzyme lacks chiral specificity and thus hydrolyzes both toxic and non-toxic soman stereoisomers at equal rates. The enzyme activity is stable at low temperature, found almost exclusively in the soluble fraction of these cells, and enhanced significantly by Mn2+ and by chemical differentiation of these cells in culture. The results suggest possible application of this enzyme for soman detection and/or detoxication, and use of the NG108-15 cell line to study the natural function(s) of enzymes of this type.
Large prospective studies and intervention trials have identified major risk factors for premature heart disease in men, while the Framingham Heart Disease Study has provided the leading evidence of predictors of cardiovascular disease in women. We evaluated the role of these risk factors in a 13-year follow-up study of 8935 premenopausal and 2716 postmenopausal women in the Walnut Creek Contraceptive Drug Study cohort in Northern California. Elevated cholesterol levels, high blood pressure, smoking, obesity, family history of heart disease, and diabetes were investigated for their contribution to premature death due to all causes and due to cardiovascular disease. In addition, risk factor profiles were developed separately for users and nonusers of Premarin (conjugated estrogen) in the postmenopausal cohort. The results show that the strongest predictors of cardiovascular mortality among premenopausal women were smoking, high blood pressure, and diabetes, with relative risks of 2.8, 10.5, and 11.6, respectively. A disparity between high cardiovascular risk factor prevalence and low rates of premature heart disease indicates that the high relative risks will not be accompanied by large attributable risks. Nevertheless, the study reconfirms the need for screening women for heart disease risk because life-style changes can improve cardiovascular risk factors and can potentially reduce the chance of premature death even further.
The joint effects of conjugated estrogen use, age, body mass index, and smoking on plasma lipid and lipoprotein levels were assessed in 585 women who used oral estrogen and 1093 women who did not who participated in the Walnut Creek Contraceptive Drug Study. Whether administered daily or cyclically, conjugated estrogen was associated with reductions in low-density lipoprotein cholesterol levels and increases in high-density lipoprotein cholesterol and triglyceride levels. The adjusted mean low-density lipoprotein cholesterol concentration was 132 mg/dl for women who used conjugated estrogen in a dose greater than or equal to 1.25 mg/day; the adjusted corresponding mean concentration was 147 mg/dl for postmenopausal women who did not use estrogen. A dose-response pattern was demonstrated between conjugated estrogen and low- and high-density lipoprotein cholesterol levels. A maximum low-density lipoprotein cholesterol level reduction was reached at a dose of 1.25 mg, suggesting a saturation phenomenon. Stepwise dose-response increases in high-density lipoprotein cholesterol levels were also found with estrogen therapy, with a maximum increase of 8 to 10 mg/dl observed with the 1.25 mg dose. Estrogen-related rises in low-density lipoprotein cholesterol levels and decreases in high-density lipoprotein cholesterol levels were offset by 2 to 3 mg/dl in women who smoked. It may be concluded, therefore, that among postmenopausal women, low-risk lipoprotein profiles as assessed by low- and high-density lipoprotein cholesterol levels are found in nonsmokers whose postmenopausal hormone therapy includes the equivalent of a conjugated estrogen dose of 1.25 mg.
Envelope glycoproteins of human parainfluenza virus type 3 (PIV-3) were selectively solubilized with n-octyl beta-D-glucopyranoside and reconstituted into lipid vesicles by dialysis of the detergent. The efficacy of the glycoprotein preparation as a subunit vaccine when administered to hamsters intranasally or subcutaneously was compared. Animals receiving four intranasal immunizations with 5 micrograms of the glycoprotein preparation were completely resistant to challenge infection. Only partial protection, however, was observed in animals immunized subcutaneously with the same dose of antigen. The local glycoprotein-specific IgA response was significantly higher in intranasally immunized animals and was implicated in resistance to challenge infection.
Affinity-purified hemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins of human parainfluenza virus type 3 (P13 virus) were used to investigate their role in the induction of a protective immune response following immunization of hamsters. The efficacy of immunization with the glycoprotein antigens was tested by challenge infection. Results of virus recovery from lungs and trachea demonstrated that although immunization with HN or F alone induced an antibody response to the respective glycoproteins, it did not provide a significant level of protection. However, immunization with a mixture of both purified glycoproteins induced higher virus-neutralizing activity in bronchial lavages and afforded complete protection from challenge infection. Similarly, incomplete protection was observed after passive transfer of monospecific rabbit antibody to the purified HN or F in baby hamsters. On the other hand, passive transfer of a mixture of antibodies to HN and F conferred a higher level of protection. Thus, the presence of antibody to both glycoproteins of P13 virus may be essential for protective immunity.
Over a 6-month period 124 patients submitted to aortic or infra-inguinal arterial reconstruction were alternately allocated to receive cloxacillin plus gentamicin (CX/GM) for 48 hours or cefotaxime (CTX) for 24 hours perioperatively. Evaluations during during the first month were performed by a blinded independent observer and patients were followed for between 6 and 20 months. 63 patients received CX/GM and 61 CTX; the groups were matched for sepsis risk factors. Sepsis rates were: groin and abdominal wounds, CX/GM 5.4% (7 of 129), CTX 6.2% (8 of 127); graft, CX/GM 1.5% (1 of 63), CTX 3.3% (2 of 61). The differences were not statistically significant (p greater than 0.05). Virtually all wound infections were superficial (class I) and no late infections have emerged. 56 patients had infected extremity lesions and 68 had no lesion. There was no significant difference in wound or graft sepsis rates between the 2 groups. Positive cultures of groin lymph nodes and/or aortic clot or atheroma did not predispose patients to postoperative sepsis. The organisms cultured from the extremity lesions were not found in infected wounds of abdominal surgery patients. However, species type and antibiotic susceptibility patterns suggest that the same pathogens were present in wound infections as were isolated from the extremity lesions of patients who underwent infra-inguinal surgery. Thus direct, rather than lymphatic, contamination may be the major aetiological factor. Most infecting organisms were susceptible to the antibiotic used.
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Radioactive glycerol, ethanolamine, or choline injected into the vicinity of the cell bodies of rat sciatic nerve sensory fibers is incorporated into phospholipid. Some newly synthesized ethanolamine and choline phosphoglycerides are subsequently committed to transport down the sciatic nerve axons at a rate of several hundred millimeters per day. Most labeled choline phosphoglycerides move uniformly down the axons; in contrast, the crest of moving ethanolamine phosphoglycerides is continually attenuated. These data, as well as differences in the clearance of these phospholipids distal to a nerve ligature, suggest that various classes of labeled phospholipids are differentially unloaded from the transport vector (possibly by exchange with unlabeled lipid in stationary axonal structures) during movement down the axons. The extent of unloading appears to be defined by the base moiety; both diacyl and plasmalogen species of ethanolamine phosphoglycerides exchange extensively with stationary axonal lipids, while most choline phosphoglycerides continue down the axons. Autoradiographic studies with 3H-choline and 3H-ethanolamine demonstrated that most unloaded phospholipid is initially deposited in axonal structures; some of this unloaded lipid is subsequently transferred to the axon/myelin interface (axolemma?) and then to myelin. Although transported ethanolamine phosphoglycerides exchange more extensively with lipids in stationary axonal structures than do choline phosphoglycerides, at early times more label from 3H-choline is found in myelin. A model to resolve this seeming discrepancy is proposed, wherein a differential topographic localization of phospholipid classes in the membrane of the transport vector allows for a preferential extensive exchange of transported ethanolamine phosphoglycerides with lipids in stationary axonal structures, while choline phosphoglycerides become available for rapid transfer to myelin by a process involving vesicle fusion with axolemma.
Choleraphage phi 149 receptor activity was found in the outer membrane (OM) protein of Vibrio cholerae 154. Receptor protein for phage phi 149 was separated from trypsin-treated OM on a Sephadex G-100 column. Of the three peaks obtained, phage receptor activity was noted only in peak II. SDS-PAGE showed that the Mr of the protein was 35,000. The protein was heat-labile and protease-sensitive. The specificity of this protein as choleraphage phi 149 receptor was investigated by carrying out a protection experiment by anti-protein (peak II) rabbit sera.
The 5.8S and 5S rRNA components from the FCR-3/The Gambia strain of Plasmodium falciparum have been identified and the complete nucleotide sequence of a 5.8S ribosomal RNA gene determined. Unlike the 5S rRNA species, the 5.8S is a single homogeneous population of molecules of 157 nucleotides. Comparison of its nucleotide sequence with previously reported 5.8S rRNA sequences indicates that it is homologous to these molecules, but distantly related to them. The sequence of the 5.8S rRNA coding region from the pfrib-2 recombinant of the HG13 Gambian isolate of P. falciparum is identical.
Diospyrin, a bis-naphthoquinone derivative, isolated from a plant, known for its antitumour properties against Ehrlich ascites carcinoma in Swiss A mice, exhibits antiprotozoal activity towards L. donovani promastigotes in culture.
Mithramycin induces a reversible inhibition of cellular RNA synthesis without affecting DNA synthesis. The authors have shown this drug induces myeloid differentiation of HL-60 promyelocytic leukemia cells and is an effective agent in certain patients with chronic granulocytic leukemia. In order to investigate the mechanism by which this drug inhibits RNA synthesis we have compared the effect of mithramycin on RNA synthesis by whole cells, isolated nuclei, and RNA synthesis by isolated E. coli RNA polymerase and eukaryotic RNA polymerase II. Exposure of HL-60 cells to mithramycin at concentrations of 4.6 X 10(-7) m or higher for 48 hours causes an almost immediate inhibition of RNA synthesis (up to 85% at 4 hours) with only modest cytotoxicity at these concentrations. Endogenous RNA synthesis by isolated nuclei can be inhibited by mithramycin only at high concentrations (greater than 10(-5) m), suggesting that mithramycin primarily may inhibit initiation, rather than elongation. Mithramycin inhibits in vitro transcription of salmon sperm DNA by E. coli RNA polymerase at DNA:drug ratios similar to those required for RNA synthesis inhibition in whole cells. Similar DNA binding studies with synthetic oligonucleotides demonstrate that mithramycin is a potent inhibitor of transcription of Poly dG.dC by E. coli RNA polymerase but has no effect on transcription of Poly dA.dT. The rapid inhibition of whole cell and isolated RNA polymerase transcription, and the relative insensitivity of isolated nuclei, suggest mithramycin may interact with specific DNA sequences in order to inhibit the initiation of RNA synthesis in intact cells.
Monoclonal antibodies to the envelope glycoproteins, HN and F, of human parainfluenza virus type 3 were coupled to a Sepharose 4B matrix and used for affinity purification of the viral glycoproteins. The purity of the glycoproteins was demonstrated by SDS-PAGE followed by fluorography or silver staining. The antigenicity of the glycoproteins was determined by immunization of rabbits; polyclonal rabbit antisera demonstrated inhibition of functional activities of the virus glycoproteins. The F glycoprotein, when reconstituted into lipid vesicles, showed distinct spike-like projections similar to those of intact virions.